Tuberculosis (TB) infection is the leading cause of death in the setting of AIDS. Of the estimated 42 million human immunodeficiency virus type 1 (HIV-1)-infected individuals globally, over 11 million are also co-infected with Mycobacterium tuberculosis (MTb). In the HIV-1/MTb co-infected host, the pathogenesis and outcome of each infection is greatly influenced by the other. Cambodia, which is one of the highest TB burdened countries globally, also has the highest prevalence of HIV-1 infection in Southeast Asia. Despite the morbidity and mortality due to clinical TB in the setting of AIDS, optimal therapeutic guidelines for treatment have not been established. Our hypothesis, to be tested in a clinical trial in Aim 1, is that the timing of (antiretroviral) ARV therapy in AIDS patients with TB and a low CD4 count impacts morbidity and mortality caused by co-infection. The goal of Aim 2 is to develop clinical Centers of Excellence in urban and rural settings that will pioneer models of HIV and TB care. These centers will be devoted to building the clinical, laboratory and infrastructure capacity to establish a clinical and research network for HIV and TB in Cambodia. The goals of Aim 3, the characterization of host genetic and immune factors that influence clinical outcome in TB and HIV-1 co-infection will provide a detailed understanding of the pathogenesis of HIV-1/TB co-infection in Cambodia and will build technical research capacity within the country. The Cambodian CIPRA planning process and the long term collaborative relationships between several members of the CIPRA group has forged a powerful team to effect capacity building on HIV and TB care at the national level as well as to accomplish the specific aims of this application. This unique and powerful group of clinicians, scientists and care-givers working collaboratively, has the expertise and capacity to achieve the proposed scientific, clinical, and training goals that will result in the creation of a comprehensive, integrated clinical program for HIV and TB therapy in Cambodia. The development of Cambodian research capacity and the infrastructure needed to address the immunological, bacteriological and virological factors involved in pathogenesis of TB/AIDS co-infection, will allow the testing of novel therapeutic and vaccines for the treatment and prevention of AIDS and TB in Cambodia as they are developed